Chronic pancreatitis is a painful disorder characterized by fibrosis and destruction of the normal pancreatic architecture. Alcohol abuse is the most common etiologic factor of chronic pancreatitis, resulting in over 70- 80% of cases. An improved understanding of the pathogenesis of alcohol induced pancreatic injury are needed to: 1) assess the benefits of therapy directed at modifying or retarding disease progression, 2) identify patients at risk for long term complications such as malabsorption and diabetes and to 3) assist in the safe and accurate evaluation of abdominal pain syndromes often misinterpreted as chronic pancreatitis. The objective of this proposal is to study the effects of alcohol on the proteomic secretory profile of pancreatic fluid in various stages of chronic alcohol induced pancreatitis. The analysis of the global proteome of any complex body fluid is challenging, but emerging proteomic technologies are playing an essential role in mechanistic studies and in the search for useful biomarkers of disease. Pancreatic fluid is an excellent specimen for the identification of novel proteins since it has a low complexity compared to serum and may be a rich source of low-abundant proteins which are potentially up- or down regulated in chronic pancreatitis. We plan to test the following overall HYPOTHESIS: Alcohol induces changes in the pancreas fluid protein profile that reflect the progressive scarring, inflammation and fibrosis that leads to end organ damage such as malabsorption, diabetes and cancer. To test our hypothesis and achieve our objective we have developed a virtually risk-free endoscopic collection procedure, established a robust preparation method and a refined sample handling technique to generate reproducible protein profiles in pancreatic fluid. SPECIFIC AIMS: (1) To Develop Cohorts and Collect Pancreatic Fluid for Proteomic Profiling of Alcohol- induced Chronic Pancreatitis. (2) To Determine the Protein Profile of Pancreatic Fluid in Healthy Controls, Alcohol-induced Acute Pancreatitis, and Patients with Alcohol-induced Chronic Pancreatitis. The complete proteome of collected pancreatic fluid from each cohort will be determined using state-of-the-art proteomic technology. The qualitative and quantitative differences, molecular function and cellular origin of identified proteins will be compared to investigate the effect of alcohol on the proteomic secretory profile of pancreatic fluid. SIGNIFICANCE: Identifying the unique protein patterns associated with chronic pancreatitis disease severity / dysfunction within the pancreatic fluid may illuminate the mechanisms of alcohol induced pancreas injury. PUBLIC HEALTH RELEVANCE: We hypothesize that alcohol induces changes in the pancreas fluid protein profile that reflect the progressive scarring, inflammation and fibrosis that leads to end organ damage. To test our hypothesis and achieve our objective we have developed a virtually risk-free endoscopic collection procedure, established a robust preparation method and a refined sample handling technique to generate reproducible protein profiles in pancreatic fluid. Identifying the unique protein patterns associated with chronic alcohol induced pancreatic disease severity within the pancreatic fluid may illuminate the mechanisms of alcohol induced pancreas injury.